Risk Assessment, Genetic Counseling, and Genetic Testing for BRCA1/2-Related Cancer in Women: A Systematic Review for the U.S. Preventive Services Task Force [Entered Retrospectively]

Project Summary Title and Description

Title
Risk Assessment, Genetic Counseling, and Genetic Testing for BRCA1/2-Related Cancer in Women: A Systematic Review for the U.S. Preventive Services Task Force [Entered Retrospectively]
Description
Background: Pathogenic mutations in breast cancer susceptibility genes BRCA1 and BRCA2 increase risks for breast, ovarian, fallopian tube, and peritoneal cancer in women; interventions reduce risk in mutation carriers. Purpose: To update the 2013 U.S. Preventive Services Task Force review on benefits and harms of risk assessment, genetic counseling, and genetic testing for BRCA1/2-related cancer in women. Data Sources: Cochrane libraries; MEDLINE, PsycINFO, EMBASE (January 1, 2013 to March 6, 2019 for updates; January 1, 1994 to March 6, 2019 for new key questions and populations); reference lists. Study Selection: Discriminatory accuracy studies, randomized controlled trials (RCTs), and observational studies of women without recently diagnosed BRCA1/2-related cancer. Data Extraction: Data on study methods; setting; population characteristics; eligibility criteria; interventions; numbers enrolled and lost to followup; outcome ascertainment; and results were abstracted. Two reviewers independently assessed study quality. Data Synthesis (Results): 103 studies (110 articles) were included. No studies evaluated the effectiveness of risk assessment, genetic counseling, and genetic testing in reducing incidence and mortality of BRCA1/2-related cancer. Fourteen studies of 10 risk assessment tools to guide referrals to genetic counseling demonstrated moderate to high accuracy (area under the receiver operating characteristic curve 0.68 to 0.96). No studies determined optimal ages, frequencies, or harms of risk assessment. Twenty-eight studies indicated genetic counseling is associated with reduced breast cancer worry, anxiety, and depression; increased understanding of risk; and decreased intention for testing. A RCT showed that population-based testing of Ashkenazi Jews detected more BRCA1/2 mutations than family-history based testing, while measures of anxiety, depression, distress, uncertainty, and quality of life were similar between groups; clinical outcomes were not evaluated. Twenty studies indicated breast cancer worry and anxiety were higher after testing for women with positive results and lower for others, and understanding of risk was higher. No RCTs evaluated the effectiveness of intensive screening for breast or ovarian cancer in mutation carriers. In observational studies, false-positive rates, additional imaging, and benign biopsies were higher with magnetic resonance imaging than mammography. In eight RCTs, tamoxifen (risk ratio [RR], 0.69; 95% confidence interval [CI], 0.59 to 0.84; 4 trials), raloxifene (RR, 0.44 95% CI, 0.24 to 0.80; 2 trials), and aromatase inhibitors (RR, 0.45 95% CI, 0.26 to 0.70; 2 trials) were associated with lower risks of invasive breast cancer compared with placebo; results were not specific to mutation carriers. Adverse effects included venous thromboembolic events for tamoxifen and raloxifene; endometrial cancer and cataracts for tamoxifen; and vasomotor, musculoskeletal, and other symptoms for all medications. In observational studies, mastectomy was associated with 90 to 100 percent reduction in breast cancer incidence and 81 to 100 percent reduction in breast cancer mortality; oophorectomy or salpingo-oophorectomy was associated with 69 to 100 percent reduction in ovarian cancer; complications were common with mastectomy. Limitations: Including only English-language articles and studies applicable to the United States; varying number, quality, and applicability of studies; and few studies of untested women previously treated for BRCA1/2-related cancer. Conclusions: Risk assessment, genetic counseling, and genetic testing to reduce BRCA1/2-cancer incidence and mortality as a prevention service has not been directly evaluated by current research. Risk assessment with familial risk tools accurately identifies high-risk women for genetic counseling. Genetic counseling reduces breast cancer worry, anxiety, and depression; increases understanding of risk; and decreases intention for mutation testing, while testing improves accuracy of understanding of risk. The effectiveness of intensive screening is not known, but it increases false-positive results and procedures. Risk-reducing medications and surgery are associated with reduced breast and ovarian cancer, but also have adverse effects. Evidence gaps relevant to prevention remain and additional studies are needed to better inform clinical practice.
Attribution
N/A
Authors of Report
N/A
Methodology description
Study Selection: Discriminatory accuracy studies, randomized controlled trials (RCTs), and observational studies of women without recently diagnosed BRCA1/2-related cancer. Data Extraction: Data on study methods; setting; population characteristics; eligibility criteria; interventions; numbers enrolled and lost to followup; outcome ascertainment; and results were abstracted. Two reviewers independently assessed study quality.
PROSPERO
N/A
DOI
10.26300/0f6g-jg52
Notes
Data was entered retrospectively via the upload of the evidence and quality appendix tables in a single Word file. The tables uploaded for this project include: Appendix B Table 1. Quality Assessment of Diagnostic Accuracy Studies Appendix B Table 2. Quality Assessment of Randomized Controlled Trials Appendix B Table 3. Quality Assessment of Cohort Studies Appendix B Table 4. Quality Assessment of Single Arm Cohort Studies Appendix B Table 5. Quality Assessment of Case-Control Studies Appendix B Table 6. Quality Assessment of Systematic Review Appendix B Table 7. Evidence Table of Genetic Counseling Studies Appendix B Table 8. Evidence Table of Genetic Testing Studies Appendix B Table 9. Evidence Table of Studies of Intensive Screening Interventions Appendix B Table 10. Evidence Table of Risk-reducing Surgery Studies Appendix B Table 11. Evidence Table of Psychological and Sexual Functioning Harms of Intensive Screening Interventions Appendix B Table 12. Evidence Table of Physical Harms of Intensive Screening Interventions Appendix B Table 13. Evidence Table of Psychological and Sexual Functioning Harms of Risk-Reducing Surgery Appendix B Table 14. Evidence Table of Harms of Risk-Reducing Surgery
Funding Source
This report is based on research conducted by the Pacific Northwest Evidence-based Practice Center (EPC) under contract to the Agency for Healthcare Research and Quality (AHRQ), Rockville, MD (Contract No. HHSA290201500009I, Task Order No. 7)

Key Questions

1. 1. In women with unknown BRCA1/2 mutation status, does risk assessment, genetic counseling, and genetic testing result in reduced incidence of BRCA1/2-related cancer and cause-specific and all-cause mortality?
2. 2a. What is the accuracy of familial risk assessment for BRCA1/2-related cancer when performed by a nonspecialist in genetics in a clinical setting? What are the optimal ages and intervals for risk assessment? 2b. What are the benefits of pre-test genetic counseling in determining eligibility for genetic testing for BRCA1/2-related cancer? (Includes improved accuracy of risk assessment and pretest probability for testing and improved patient knowledge, understanding of benefits and harms of interventions to reduce risk, risk perception, satisfaction, and health and psychological outcomes.) 2c. What are optimal testing approaches to determine the presence of pathogenic BRCA1/2 mutations in women at increased risk for BRCA1/2-related cancer? (Includes testing other high-risk family members, including men, before testing the index patient and using specific types of tests or multigene panels.) 2d. What are optimal post-test counseling approaches to interpret results and determine eligibility for interventions to reduce risk of BRCA1/2-related cancer? (Includes improved patient knowledge, understanding of benefits and harms of interventions to reduce risk, risk perception, satisfaction, and health and psychological outcomes.)
3. 3. What are adverse effects of a) risk assessment, b) pre-test genetic counseling, c) genetic testing, and d) post-test counseling for BRCA1/2-related cancer? (Includes inaccurate risk assessment; inappropriate testing; false-positive and false-negative results; adverse effects on the patient’s family relationships; overdiagnosis and overtreatment; false reassurance; incomplete testing; misinterpretation of test results; anxiety; cancer worry; and ethical, legal, and social implications.)
4. 4. Do interventions reduce the incidence of BRCA1/2-related cancer and mortality in women at increased risk? (Includes intensive screening [earlier and more frequent screening; use of additional screening methods], use of risk-reducing medications [aromatase inhibitors; tamoxifen; raloxifene], and risk-reducing surgery [mastectomy; salpingo-oophorectomy; other procedures] when performed for prevention purposes.)
5. 5. What are adverse effects of interventions to reduce risk for BRCA1/2-related cancer? (Includes immediate and long-term harms associated with screening, risk-reducing medications, and risk-reducing surgery and ethical, legal, and social implications.)

Associated Extraction Forms

Associated Studies (each link opens a new tab)

TitleAuthorsYear
Predictors of and satisfaction with bilateral prophylactic mastectomy.1995
Screening for early familial ovarian cancer with transvaginal ultrasonography and colour blood flow imaging.1993
Psychosocial functioning in women who have undergone bilateral prophylactic mastectomy.2004
Impact of screening for breast cancer in high-risk women on health-related quality of life.2004
Efficacy of MRI and mammography for breast-cancer screening in women with a familial or genetic predisposition.2004
Screening with magnetic resonance imaging and mammography of a UK population at high familial risk of breast cancer: a prospective multicentre cohort study (MARIBS).-- Not Found --
Differences between first and subsequent rounds of the MRISC breast cancer screening program for women with a familial or genetic predisposition.2006
The course of distress in women at increased risk of breast and ovarian cancer due to an (identified) genetic susceptibility who opt for prophylactic mastectomy and/or salpingo-oophorectomy.2007
No efficacy of annual gynaecological screening in BRCA1/2 mutation carriers; an observational follow-up study.2007
Prophylactic mastectomy in BRCA1/2 mutation carriers and women at risk of hereditary breast cancer: long-term experiences at the Rotterdam Family Cancer Clinic.2007
Aesthetic outcome, patient satisfaction, and health-related quality of life in women at high risk undergoing prophylactic mastectomy and immediate breast reconstruction.2008
Psychological reactions, quality of life, and body image after bilateral prophylactic mastectomy in women at high risk for breast cancer: a prospective 1-year follow-up study.2008
Fatigue and quality of life after risk-reducing salpingo-oophorectomy in women at increased risk for hereditary breast-ovarian cancer.2009
Short-term surgical outcome and safety of risk reducing salpingo-oophorectomy in BRCA1/2 mutation carriers.2010
High satisfaction rate ten years after bilateral prophylactic mastectomy - a longitudinal study.2011
Bilateral prophylactic mastectomy in women with inherited risk of breast cancer--prevalence of pain and discomfort, impact on sexuality, quality of life and feelings of regret two years after surgery.2010
The impact of prophylactic salpingo-oophorectomy on menopausal symptoms and sexual function in women who carry a BRCA mutation.2011
Effectiveness of alternating mammography and magnetic resonance imaging for screening women with deleterious BRCA mutations at high risk of breast cancer.2011
Bilateral prophylactic mastectomy in Swedish women at high risk of breast cancer: a national survey.2011
Psychological impact of recall on women with BRCA mutations undergoing MRI surveillance.2011
Less correspondence between expectations before and cosmetic results after risk-reducing mastectomy in women who are mutation carriers: a prospective study.2012
Body image and psychological distress after prophylactic mastectomy and breast reconstruction in genetically predisposed women: a prospective long-term follow-up study.2012
Long-term psychological distress in women at risk for hereditary breast cancer adhering to regular surveillance: a risk profile.2013
Body image issues after bilateral prophylactic mastectomy with breast reconstruction in healthy women at risk for hereditary breast cancer.2013
The psychological impact of breast and ovarian cancer preventive options in BRCA1 and BRCA2 mutation carriers.2014
Effects of false-positive cancer screenings and cancer worry on risk-reducing surgery among BRCA1/2 carriers.2015
Patient experience with breast reconstruction process following bilateral mastectomy in BRCA mutation carriers.2017
Multidisciplinary management of risk-reducing mastectomy and immediate reconstruction: treatment algorithm and patient satisfaction2015
Association of risk-reducing surgery in BRCA1 or BRCA2 mutation carriers with cancer risk and mortality.
Risk reducing mastectomy: outcomes in 10 European centres.2009
Efficacy of bilateral prophylactic mastectomy in women with a family history of breast cancer.1999
Efficacy of bilateral prophylactic mastectomy in BRCA1 and BRCA2 gene mutation carriers.
Prophylactic oophorectomy reduces breast cancer penetrance during prospective, long-term follow-up of BRCA1 mutation carriers.2005
Bilateral oophorectomy and breast cancer risk reduction among women with a family history.2004
Breast cancer after bilateral risk-reducing mastectomy.2011
Prophylactic oophorectomy in inherited breast/ovarian cancer families.1995
Surgical Decision Making in the BRCA-Positive Population: Institutional Experience and Comparison with Recent Literature.-- Not Found --
Breast cancer risk after salpingo-oophorectomy in healthy BRCA1/2 mutation carriers: revisiting the evidence for risk reduction.2015
Substantial breast cancer risk reduction and potential survival benefit after bilateral mastectomy when compared with surveillance in healthy BRCA1 and BRCA2 mutation carriers: a prospective analysis.2013
Cancer risks for BRCA1 and BRCA2 mutation carriers: results from prospective analysis of EMBRACE.2013
Prospective study of breast MRI in BRCA1 and BRCA2 mutation carriers: effect of mutation status on cancer incidence.2009
Bilateral Oophorectomy and Breast Cancer Risk in BRCA1 and BRCA2 Mutation Carriers.2017
Prophylactic oophorectomy in carriers of BRCA1 or BRCA2 mutations.2002
Predicting the likelihood of carrying a BRCA1 or BRCA2 mutation: validation of BOADICEA, BRCAPRO, IBIS, Myriad and the Manchester scoring system using data from UK genetics clinics.2008
Development and validation of a simple questionnaire for the identification of hereditary breast cancer in primary care.2009
Assessing BRCA carrier probabilities in extended families.2006
Validation of a tool for identifying women at high risk for hereditary breast cancer in population-based screening.2006
Application of BRCA1 and BRCA2 mutation carrier prediction models in breast and/or ovarian cancer families of French Canadian descent.2006
Selecting a BRCA risk assessment model for use in a familial cancer clinic.2008
A two-stage approach to genetic risk assessment in primary care.2016
Evaluating the performance of the breast cancer genetic risk models BOADICEA, IBIS, BRCAPRO and Claus for predicting BRCA1/2 mutation carrier probabilities: a study based on 7352 families from the German Hereditary Breast and Ovarian Cancer Consortium.2013
Validation of the Manchester scoring system for predicting BRCA1/2 mutations in 9,390 families suspected of having hereditary breast and ovarian cancer.2014
Validation of the pedigree assessment tool (PAT) in families with BRCA1 and BRCA2 mutations.2010
Validity of models for predicting BRCA1 and BRCA2 mutations.2007
A preliminary validation of a family history assessment form to select women at risk for breast or ovarian cancer for referral to a genetics center.2000
A new scoring system for the chances of identifying a BRCA1/2 mutation outperforms existing models including BRCAPRO.2004
Evaluation of a breast/ovarian cancer genetics referral screening tool in a mammography population.2009
Racial differences in the use of BRCA1/2 testing among women with a family history of breast or ovarian cancer.2005
Psychological factors associated with emotional responses to receiving genetic risk information.2008
Factors associated with intrusive cancer-related worries in women undergoing cancer genetic risk assessment.2009
Effects of a telephone counseling intervention on sisters of young women with breast cancer.2006
Effects of counseling Ashkenazi Jewish women about breast cancer risk.2006
A randomized trial of specialist genetic assessment: psychological impact on women at different levels of familial breast cancer risk.2002
The evolution of worry after breast cancer risk assessment: 6-year follow-up of the TRACE study cohort.2011
Development of a risk assessment tool for women with a family history of breast cancer.2005
A randomised controlled trial of breast cancer genetics services in South East Scotland: psychological impact.2003
Patients' resistance to risk information in genetic counseling for BRCA1/2.2005
Results of a randomized study of telephone versus in-person breast cancer risk counseling.2006
Psychological support needs for women at high genetic risk of breast cancer: some preliminary indicators.-- Not Found --
A randomised comparison of UK genetic risk counselling services for familial cancer: psychosocial outcomes.2004
Subjective and objective risk of ovarian cancer in Ashkenazi Jewish women testing for BRCA1/2 mutations.2008
A randomized trial of breast cancer risk counseling: interacting effects of counseling, educational level, and coping style.1996
Communication and information-giving in high-risk breast cancer consultations: influence on patient outcomes.2004
Healthy women with a family history of breast cancer: impact of a tailored genetic counseling intervention on risk perception, knowledge, and menopausal therapy decision making.2006
Risk perception among women receiving genetic counseling: a population-based follow-up study.2007
Psychosocial consequences of genetic counseling: a population-based follow-up study.-- Not Found --
Longer-term influence of breast cancer genetic counseling on cognitions and distress: smaller benefits for affected versus unaffected women.2011
Does enhanced information at cancer genetic counseling improve counselees' knowledge, risk perception, satisfaction and negotiation of information to at-risk relatives?--a randomized study.2009
A systematic review of the impact of genetic counseling on risk perception accuracy.2009
Family history of breast cancer: what do women understand and recall about their genetic risk?1998
The impact of genetic counselling on risk perception and mental health in women with a family history of breast cancer.1999
The use of videotaped information in cancer genetic counselling: a randomized evaluation study.1998
Genetic counseling for women with an intermediate family history of breast cancer.2000
Effects of risk counseling on interest in breast cancer genetic testing for lower risk women.-- Not Found --
Racial differences in testing motivation and psychological distress following pretest education for BRCA1 gene testing.
Breast cancer risk counseling improves women's functioning.2004
Counselees' Expressed Level of Understanding of the Risk Estimate and Surveillance Recommendation are Not Associated with Breast Cancer Surveillance Adherence.2016
Population testing for cancer predisposing BRCA1/BRCA2 mutations in the Ashkenazi-Jewish community: a randomized controlled trial.2015
Evaluation of psychosocial effects of pre-symptomatic testing for breast/ovarian and colon cancer pre-disposing genes: a 12-month follow-up.2004
Quality of life in asymptomatic BRCA1/2 mutation carriers.2009
Identification of patients at high risk of psychological distress after BRCA1 genetic testing.2009
Predictive genetic testing for BRCA1/2 in a UK clinical cohort: three-year follow-up.2007
The relationship between coping strategies and anxiety in women from families with familial breast-ovarian cancer in the absence of demonstrated mutations.2008
Psychological distress in women at risk of hereditary breast/ovarian or HNPCC cancers in the absence of demonstrated mutations.2005
Long-term psychosocial outcomes of BRCA1/BRCA2 testing: differences across affected status and risk-reducing surgery choice.2012
Cancer risk management strategies and perceptions of unaffected women 5 years after predictive genetic testing for BRCA1/2 mutations.2011
The impact of receiving genetic test results on general and cancer-specific psychologic distress among members of an African-American kindred with a BRCA1 mutation.2005
Benefit finding in response to BRCA1/2 testing.2008
Psychological impact of genetic testing in women from high-risk breast cancer families.2002
Long-term follow-up of Jewish women with a BRCA1 and BRCA2 mutation who underwent population genetic screening.2012
BRCA1 testing with definitive results: a prospective study of psychological distress in a large clinic-based sample.2004
Psychological and cancer-specific distress at 18 months post-testing in women with demonstrated BRCA1 mutations for hereditary breast/ovarian cancer.2008
Sleep disturbances in asymptomatic BRCA1/2 mutation carriers: women at high risk for breast-ovarian cancer.2010
Clinical characteristics affect the impact of an uninformative DNA test result: the course of worry and distress experienced by women who apply for genetic testing for breast cancer.2006
Factors associated with an individual's decision to withdraw from genetic testing for breast and ovarian cancer susceptibility: implications for counseling.2007
Psychological impact of genetic testing for breast cancer susceptibility in women of Ashkenazi Jewish background: a prospective study.2004
Familial context of genetic testing for cancer susceptibility: moderating effect of siblings' test results on psychological distress one to two weeks after BRCA1 mutation testing.1999
Population screening for BRCA1/BRCA2 founder mutations in Ashkenazi Jews: proactive recruitment compared with self-referral.2017
Long-term psychological impact of carrying a BRCA1/2 mutation and prophylactic surgery: a 5-year follow-up study.2003
Impact of Panel Gene Testing for Hereditary Breast and Ovarian Cancer on Patients.2017

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